One‐Pot Facile Encapsulation of Dimethyloxallyl Glycine by Nanoscale Zeolitic Imidazolate Frameworks‐8 for Enhancing Vascularized Bone Regeneration

• Published in: Advanced healthcare materials 2023-02, Vol.12 (4), p.e2202317-n/a
• Main Authors: Zhang, Xin, Chen, Jun‐Yu, Pei, Xiang, Li, Ya‐Hong, Feng, Hao, He, Zi‐Han, Xie, Wen‐Jia, Pei, Xi‐Bo, Zhu, Zhou, Wan, Qian‐Bing, Wang, Jian
• Format: Article
• Language: English
• Subjects: Alkaline phosphatase; Angiogenesis; Bone growth; Bone marrow; Bone Regeneration; Computed tomography; Coupling; Defects; dimethyloxallyl glycine; drug loading; Endothelial Cells; Extracellular matrix; Glycine; Humans; Immunofluorescence; In vitro methods and tests; Mesenchyme; Metal-organic frameworks; Mineralization; Nanoparticles; Osteogenesis; Proteins; Regeneration; Regeneration (physiology); Stem cells; Tissue engineering; Umbilical vein; vascularization; Zeolites; Zeolites - pharmacology; zeolitic imidazolate frameworks‐8
• ISSN: 2192-2640; 2192-2659
• DOI: 10.1002/adhm.202202317

In the process of bone tissue regeneration, regulation of osteogenesis–angiogenesis coupling is of great importance. Therefore, dimethyloxallyl glycine (DMOG) is loaded by nanoscale zeolitic imidazolate frameworks‐8 (ZIF‐8) to obtain a drug‐loading system that can promote osteogenesis–angiogenesis coupling. Characterization of the drug‐loading nanoparticles (DMOG@ZIF‐8) reveals that DMOG is successfully loaded into ZIF‐8 by two different methods, and the DMOG@ZIF‐8 is prepared using the one‐pot method (OD@ZIF‐8) achieves higher loading efficiency and longer release time than those prepared using the post‐loading method (PD@ZIF‐8). In vitro studies found that DMOG@ZIF‐8 significantly enhances the migration, tube formation, and angiogenesis‐related protein secretion of human umbilical vein endothelial cells as well as the extracellular matrix mineralization, alkaline phosphatase activity, and osteogenesis‐related protein secretion of bone marrow mesenchymal stem cells. Moreover, OD@ZIF‐8 nanoparticles are more efficient than PD@ZIF‐8 nanoparticles in induction of osteogenesis–angiogenesis coupling. Then, in vivo cranial critical defect model shows that the addition of OD@ZIF‐8 significantly promotes vascularized bone formation as indicated by the results including microcomputed tomographic, histological and immunofluorescence staining, and so on. Taken together, loading ZIF‐8 with DMOG may be a promising solution for critical‐sized bone defect reconstruction and the one‐pot method is preferred in the preparation of such drug‐loading system. Dimethyloxallyl glycine (DMOG)@zeolitic imidazolate frameworks‐8 (ZIF‐8) nanoparticles (NPs) are successfully synthesized by using two methods; the one‐pot method and post‐loading method. The drug‐loading NPs prepared using the one‐pot method show higher loading efficiency and slower release kinetics and contribute to better ability to promote vascularized bone regeneration. Further studies reveal that the drug‐loading NPs promote vascularized bone regeneration mainly through activation of MAPK and PI3K‐AKT signaling pathways.